The nucleosome reference frame and standard geometries for octasomes

Area of Science:

• Structural Biology
• Biophysics
• Genomics

Background:

• Over 533 nucleosome structures are available in the Research Collaboratory for Structural Bioinformatics (RCSB), encompassing diverse variants and species.
• The fundamental organization of histones and DNA within standard octasomes is highly conserved, forming the basis for structural comparisons.

Purpose of the Study:

• To establish a standardized nucleosome reference frame for describing and comparing diverse nucleosome structures.
• To rigorously differentiate between nucleosomal and linker DNA based on superhelix geometry.
• To analyze the spatial organization and dynamics of DNA within histone octamers.

Main Methods:

• Development of a nucleosome reference frame based on conserved Rise and Twist parameters.
• Analysis of DNA director frames extracted from X-ray crystal structures.
• Comparison of observed DNA superhelix parameters with ideal superhelix models.

Main Results:

• Cumulative sums of Rise, Twist, and DNA arc length are linear functions of base pair index (R² > 0.999) for octasome structures.
• Nucleosomal DNA exhibits a sinusoidal variation in superhelix radius and pitch, with a distinct straightening at the outermost turn.
• Identification of conserved 'singletrack' and variable 'multipath' regions for DNA organization around the histone octamer.

Conclusions:

• The proposed reference frame provides a rigorous method for separating nucleosomal and linker DNA.
• The conserved DNA organization near the dyad and variable regions away from it offer insights into nucleosome dynamics.
• The framework is applicable to analyzing various nucleosome structures, including standard, distorted, super-nucleosomal, and circular DNA-bound forms.